Further study of fibroblasts demonstrated that the cholinergic muscarinic receptor is capable of up-regulation, and that cholinergic agonists inhibit adenyl cyclase in the fibroblasts. Clinical genetic study of patients and ill relatives reveals significantly higher density of muscarinic binding sites than in normal controls. Genetic control of variation in binding sites and in up-regulation has been demonstrated. Other clinical biological studies show that plasma GABA is significantly reduced in euthymic medication free patients, but platelet 3H-imipramine binding is not different from normal controls. Family study data from normal controls added to data from affective patients has now shown that affective illness is highly familial, following a multifactorial (polygenic) mode of inheritance in the population. Anorexia nervosa patients have high frequency of bipolar and unipolar disorder in relatives, suggesting a genetic relation between anorexia and affective disorders.